Plasmodium falciparum is a global health problem because of the morbidity and mortality associated with infection. Much of this morbidity and mortality is believed to arise from the actions of a malaria toxin. The toxin initiates a systemic inflammatory cascade involving cytokine excess, which may result in disseminated intravascular coagulation, hepatic dysfunction, acute renal failure, multi-organ inflammation, hypoglycemia, lactic acidosis and death. The toxin may further contribute to organ-specific and cerebral disease syndromes by hyperactivation of the vascular endothelium. Clinical immunity to malaria is acquired considerably earlier than anti-parasite immunity, and it is possible that this is mediated by anti-toxin mechanisms.